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Characterization of maturation of neuronal voltage-gated sodium channels SCN1A and SCN8A in rat myocardium.

Krause U, Alflen C, Steinmetz M, Müller MJ, Quentin T, Paul T - Mol Cell Pediatr (2015)

Bottom Line: SCN1A protein level decreased after birth in contrast to RNA expression.The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life.Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiology and Intensive Care Medicine, University Medical Center, Georg August University, Göttingen, Robert-Koch-Str. 40, 37099, Göttingen, Germany. ukrause1@gwdg.de.

ABSTRACT

Background: Sodium channels predominantly expressed in brain are expressed in myocardial tissue and play an important role in cardiac physiology. Alterations of sodium channels are known to result in neurological disease in infancy and childhood. It will be of interest to study the expression of brain-type sodium channels in the developing myocardium.

Methods: The expression of neuronal sodium channels (SCN1A, SCN8A) and the cardiac isoform SCN5A in the developing rat myocardium was studied by rtPCR, Western blot, and immunohistochemistry at different stages of antenatal and postnatal development.

Results: Significant changes of sodium channel expression during development were detected. Whereas SCN5A RNA increased to maximum levels on day 21 after birth, the highest SCN1A RNA levels were detected on day 1 to 7 after birth. SCN8A RNA was maximally expressed during embryonic development. At the protein level, the amount of SCN5A protein increased along with the RNA level. SCN1A protein level decreased after birth in contrast to RNA expression. Western blot could not detect SCN8A protein in the myocardium at any stage of development. Immunohistochemistry however proved the presence of SCN8A protein in the developing rat myocardium.

Conclusions: Heart- and brain-type sodium channels are differentially expressed during ontogenesis. The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life. Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

No MeSH data available.


Related in: MedlinePlus

SCN8A mRNA expression. Highest expression of SCN8A mRNA was observed on day 17 of gestation and progressively declined after birth. Lowest levels of SCN8A mRNA were measured at age 6 weeks (Abbreviations and levels of significance as depicted in Figure 1).
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Fig3: SCN8A mRNA expression. Highest expression of SCN8A mRNA was observed on day 17 of gestation and progressively declined after birth. Lowest levels of SCN8A mRNA were measured at age 6 weeks (Abbreviations and levels of significance as depicted in Figure 1).

Mentions: In contrast to the aforementioned SCN1A and SCN5A genes, mRNA expression of the second brain-type VGSC SCN8A was highest at the embryonic stage of development and consecutively dropped after birth to 34 ± 23% on day 1 of life, to 27 ± 15% on day 7 after birth, to 11 ± 20% on day 21, and finally reached a level of 8 ± 21% in the ventricular myocardium of 6-week-old animals (Figure 3), respectively.Figure 3


Characterization of maturation of neuronal voltage-gated sodium channels SCN1A and SCN8A in rat myocardium.

Krause U, Alflen C, Steinmetz M, Müller MJ, Quentin T, Paul T - Mol Cell Pediatr (2015)

SCN8A mRNA expression. Highest expression of SCN8A mRNA was observed on day 17 of gestation and progressively declined after birth. Lowest levels of SCN8A mRNA were measured at age 6 weeks (Abbreviations and levels of significance as depicted in Figure 1).
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Related In: Results  -  Collection

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Fig3: SCN8A mRNA expression. Highest expression of SCN8A mRNA was observed on day 17 of gestation and progressively declined after birth. Lowest levels of SCN8A mRNA were measured at age 6 weeks (Abbreviations and levels of significance as depicted in Figure 1).
Mentions: In contrast to the aforementioned SCN1A and SCN5A genes, mRNA expression of the second brain-type VGSC SCN8A was highest at the embryonic stage of development and consecutively dropped after birth to 34 ± 23% on day 1 of life, to 27 ± 15% on day 7 after birth, to 11 ± 20% on day 21, and finally reached a level of 8 ± 21% in the ventricular myocardium of 6-week-old animals (Figure 3), respectively.Figure 3

Bottom Line: SCN1A protein level decreased after birth in contrast to RNA expression.The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life.Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatric Cardiology and Intensive Care Medicine, University Medical Center, Georg August University, Göttingen, Robert-Koch-Str. 40, 37099, Göttingen, Germany. ukrause1@gwdg.de.

ABSTRACT

Background: Sodium channels predominantly expressed in brain are expressed in myocardial tissue and play an important role in cardiac physiology. Alterations of sodium channels are known to result in neurological disease in infancy and childhood. It will be of interest to study the expression of brain-type sodium channels in the developing myocardium.

Methods: The expression of neuronal sodium channels (SCN1A, SCN8A) and the cardiac isoform SCN5A in the developing rat myocardium was studied by rtPCR, Western blot, and immunohistochemistry at different stages of antenatal and postnatal development.

Results: Significant changes of sodium channel expression during development were detected. Whereas SCN5A RNA increased to maximum levels on day 21 after birth, the highest SCN1A RNA levels were detected on day 1 to 7 after birth. SCN8A RNA was maximally expressed during embryonic development. At the protein level, the amount of SCN5A protein increased along with the RNA level. SCN1A protein level decreased after birth in contrast to RNA expression. Western blot could not detect SCN8A protein in the myocardium at any stage of development. Immunohistochemistry however proved the presence of SCN8A protein in the developing rat myocardium.

Conclusions: Heart- and brain-type sodium channels are differentially expressed during ontogenesis. The high expression level of SCN1A in the perinatal period and early infancy indicates its importance in preserving a regular cardiac rhythm in this early phase of life. Altered regulation of sodium channels might result in severe cardiac rhythm disturbances.

No MeSH data available.


Related in: MedlinePlus